Neighbouring Group Participation (NGP) is observed in nucleophilic substitution reactions, where a neighbouring group helps in the removal of the leaving group to form a reactive intermediate that leads to the formation of the product. Increase in the reaction rate and unexpected stereo chemical outcomes are associated in reactions involving NGP.
An atom having an unshared pair of electrons and also present at least beta to the leaving group can act as a neighbouring group. Also, NGP is mostly observed on solvolysis reactions where the solvent acts as the nucleophile.
During NGP, the neighbouring group (G) attacks the electrophilic centre to eliminate the leaving group (L). This leads to the formation of a cyclic intermediate which is very reactive. This is called anchimeric assistance from the neighbouring group. The nucleophile (Nu-)then attacks this intermediate to form the product. If the attack happens of the carbon that was having the leaving group the configuration will be retained because the configuration at that carbon will be inverted twice.
Groups like halides, hydroxides, ethers, thio ethers, amino groups, carboxylates, phenyl group, pi-bonds etc. have been indentified to act as neighbouring groups in many reactions.
The mechanism for anchimeric assistance is a two step
mechanism where two consecutive SN2 reaction leads to
retention of configuration. In the first step, the neighbouring group (Z) acts as a nucleophile,
attacking the substitution centre and expelling out the leaving group. In the next step, the external
nucleophile (Y) attack from backside displacing the neighbouring group and retaining the overall
configuration. Since the first step is slow and is rate determining, the reaction follows first order
kinetics and there is no effect of concentration of Y- on rate of reaction.
Anchimeric assistance enhances rate of reactions by several order of magnitudes. This is because
step I is the rate determining step and the neighbouring group Z which is readily available within
the substrate makes the attack much faster as compared to attack by any external nucleophile Y
for which, to react, the substrate has to collide with Y.
Since, Z is readily available by virtue of
its position its attack is much faster.
Thermodynamically also, anchimeric assistance is favoured as the reaction between the substrate
and Y- involves a large decrease in entropy of activation (∆S†), as the reactants are far less free in
the transition state than before. Reaction of Z involves a much smaller loss of entropy.
Important atoms and groups that can act as neighbouring groups are COO, COOR, COAr, OCOR, OR, OH, O, NH2, NHR, NR2, NHCOR,
SH, SR, S, SO2Ph, I, Br, and Cl.
The effectiveness of halogens as neighbouring groups decreases in the order I ,,Br, Cl. The chloride is a very weak neighbouring group and can be shown to act in this way only when the solvent does not interfere.
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Team IITian explains
24 сен 2024
